Methylation-based algorithms for diagnosis: experience from neuro-oncology

Brain tumours are the most common tumour‐related cause of death in young people. Survivors are at risk of significant disability, at least in part related to the effects of treatment. Therefore, there is a need for a precise diagnosis that stratifies patients for the most suitable treatment, matched to the underlying biology of their tumour. Although traditional histopathology has been accurate in predicting treatment responses in many cases, molecular profiling has revealed a remarkable, previously unappreciated, level of biological complexity in the classification of these tumours. Among different molecular technologies, DNA methylation profiling has had the most pronounced impact on brain tumour classification. Furthermore, using machine learning‐based algorithms, DNA methylation profiling is changing diagnostic practice. This can be regarded as an exemplar for how molecular pathology can influence diagnostic practice and illustrates some of the unanticipated benefits and risks. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

Novel therapeutic targets in epilepsy: oxidative stress and iron metabolism

Malformations of Cortical Development (MCD) are one of the most frequent causes of multidrug‐resistant focal epilepsy, of which focal cortical dysplasia type IIb (FCDIIb) and Tuberous Sclerosis

Characterization of a population of neural progenitor cells in the infant hippocampus.

Abnormalities of the hippocampus are associated with a range of diseases in children, including epilepsy and sudden death. A population of rod cells in part of the hippocampus, the polymorphic layer of the dentate gyrus, has long been recognized in infants. Previous work suggested that these cells were microglia and that their presence was associated with chronic illness and sudden infant death syndrome. Prompted by the observations that a sensitive immunohistochemical marker of microglia used in diagnostic practice does not typically stain these cells and that the hippocampus is a site of postnatal neurogenesis, we hypothesized that this transient population of cells were not microglia but neural progenitors

The 2016 World Health Organization Classification of tumours of the Central Nervous System: what the paediatric neuroradiologist needs to know

The recently published 2016 World Health Organization (WHO) classification of tumours of the Central Nervous System (CNS) introduces a number of significant changes from the previous edition. Based on an improved understanding of the genetic and molecular basis of tumorigenesis there has been a shift towards defining tumours by means of these characteristics in addition to their histological features, thus providing an integrated diagnosis. In this article, we will provide a concise overview of the salient changes in the 2016 WHO classification of tumours of the CNS that are of relevance to the paediatric neuroradiologist when it comes to day-to-day reporting

Brain weight in sudden unexpected death in infancy: experience from a large single centre cohort

Aims Published reports of brain weight in sudden infant death syndrome (SIDS) are contradictory, though several have concluded that brain weight is increased in SIDS compared to controls or reference data. This is important since, if brain weight is significantly different, it may be of diagnostic use or provide insights into the aetiology of SIDS. The aim of this study is to use a large series of well-characterised sudden unexpected infant deaths from a single centre to provide definitive data regarding this issue. Methods A retrospective review identified 1,100 infants who had died suddenly and undergone a comprehensive autopsy at Great Ormond Street Hospital between 1996 and 2011. They were split into two groups: those in whom death could be explained and those whose deaths remained unexplained despite full investigation (SIDS / unexplained SUDI). Results There were 1,100 cases of whom 573 (52%) were unexplained and 527 (48%) explained. Multiple regression analysis, which adjusted for sex, age and post-mortem interval, showed no difference in the ratio of brain weight:body weight between those infants dying of explained causes and those in whom no cause could be found. This finding remained true when restricting analysis to those with macroscopically normal brains. Conclusions In this large series of infants dying of both explained and unexplained causes, brain weight, once corrected for body weight, did not vary consistently with the cause of death. Brain weight cannot be used as a diagnostic indicator of the cause of death or to inform hypothetical models of the pathogenesis of SIDS

Developmental delay and progressive seizures in 2-month-old child with diffuse MRI abnormalities

2 month-old infant presented with seizures, radiological findings of diffuse elevated T2 signal with frontal lobe sparing and extensive symmetrical post contrast enhancement. At autopsy, the brain stem was pale and atrophic, with areas of cystic degeneration. Medullary sections showed perivascular Rosenthal fibre deposition